Safety and effectiveness of BNT162b2 mRNA Covid-19 vaccine in adolescents

In South Korea, all 12th grade students (highs school seniors) were offered BNT162b2 vaccine starting July 19, 2021; while 10^th–11th grade students were not eligible. We conducted a nationwide retrospective cohort study by to determine the safety and effectiveness of BNT162b2 mRNA Covid-19 vaccine in adolescents against SARS-CoV-2 infection. Among 444,313 persons who received the first dose of vaccine, reporting rate for myocarditis and/or pericarditis was 1.8 per 100,000 (95% C.I. 0.8–3.5) among first-dose recipients and 4.3 per 100,000 (95% C.I. 2.6–6.7) in second-dose recipients. Vaccine effectiveness against symptomatic/asymptomatic SARS-CoV-2 infection 14 days post-first dose vaccination was 91.1% (95% C.I. 89.6–92.5), and 14 days post-second dose was 99.1% (95% C.I. 98.5–99.5). In this retrospective cohort study, BNT162b2 vaccination was safe and was associated with a significantly lower risk of SARS-CoV-2 infection, suggesting that vaccination in adolescent may reduce the burden of Covid-19.     

Cohort study of Covid-19 vaccine effectiveness among healthcare workers in Finland,December 2020 - October 2021

Recently, Covid-19 vaccine effectiveness has decreased especially against mild disease due to emergence of the Delta variant and waning protection. In this register-based study among healthcare workers in Finland, the vaccine effectiveness of two-dose mRNA vaccine series against SARS-CoV-2 infection decreased from 82% (95% CI 79–85%) 14–90 days after vaccination to 53% (43–62%) after 6 months. Similar trend was observed for other series. Waning was not observed against Covid-19 hospitalization. These results facilitate decision-making of booster doses for healthcare workers.     

Effectiveness of second booster compared to first booster and protection conferred by previous SARS-CoV-2 infection against symptomatic Omicron BA.2 and BA.4/5 in France

In face of evidence of rapid waning of vaccine effectiveness against Omicron and its sub-lineages, a second booster with mRNA vaccines was recommended for the most vulnerable in France. We used a test negative design to estimate the effectiveness of the second booster relative to the first booster and the protection conferred by a previous SARS-CoV-2 infection, against symptomatic Omicron BA.2 or BA.4/5. We included symptomatic ≥60 years old individuals tested for SARS-CoV-2 in March 21-October 30, 2022. Compared to a 181–210 days old first booster, a second booster restored protection with a relative effectiveness of 41% [95%CI: 39–42%], 7–30 days post-vaccination. This gain in protection was lower than the one observed with the first booster, at equal time points since vaccination. High levels of protection were associated to previous SARS-CoV-2 infection, especially when the infection was recent and occurred when an antigenic-related variant was dominant.     

Number of COVID-19 hospitalisations averted by vaccination: Estimates for the Netherlands,January 6, 2021 through August 30, 2022

BackgroundVaccines against COVID-19 have proven effective in preventing COVID-19 hospitalisation. In this study, we aimed to quantify part of the public health impact of COVID-19 vaccination by estimating the number of averted hospitalisations. We present results from the beginning of the vaccination campaign (‘entire period’, January 6, 2021) and a subperiod starting at August 2, 2021 (‘subperiod’) when all adults had the opportunity to complete their primary series, both until August 30, 2022.MethodsUsing calendar-time specific vaccine effectiveness (VE) estimates and vaccine coverage (VC) by round (primary series, first booster and second booster) and the observed number of COVID-19 associated hospitalisations, we estimated the number of averted hospitalisations per age group for the two study periods. From January 25, 2022, when registration of the indication of hospitalisation started, hospitalisations not causally related to COVID-19 were excluded.ResultsIn the entire period, an estimated 98,170 (95 % confidence interval (CI) 96,123–99,928) hospitalisations were averted, of which 90,753 (95 % CI 88,790–92,531) were in the subperiod, representing 57.0 % and 67.9 % of all estimated hospital admissions. Estimated averted hospitalisations were lowest for 12–49-year-olds and highest for 70–79-year-olds. More admissions were averted in the Delta period (72.3 %) than in the Omicron period (63.4 %).ConclusionCOVID-19 vaccination prevented a large number of hospitalisations. Although the counterfactual of having had no vaccinations while maintaining the same public health measures is unrealistic, these findings underline the public health importance of the vaccination campaign to policy makers and the public.     

Trusted information sources in the early months of the COVID-19 pandemic predict vaccination uptake over one year later

IntroductionCOVID-19 vaccine uptake has been a major barrier to stopping the pandemic in many countries with vaccine access. This longitudinal study examined the capability to predict vaccine uptake from data collected early in the pandemic before vaccines were available.Methods493 US respondents completed online surveys both at baseline (March 2020) and wave 6 (June 2021), while 390 respondents completed baseline and wave 7 (November 2021) surveys. The baseline survey assessed trust in sources of COVID-19 information, social norms, perceived risk of COVID-19, skepticism about the pandemic, prevention behaviors, and conspiracy beliefs. Multivariable logistic models examined factors associated with the receipt of at least one COVID-19 vaccine dose at the two follow-ups.ResultsIn the adjusted model of vaccination uptake at wave 6, older age (aOR = 1.02, 95 %CI = 1.00–1.04) and greater income (aOR = 1.69, 95 %CI = 1.04–2.73) was associated with positive vaccination status. High trust in state health departments and mainstream news outlets at baseline were positively associated with vaccination at wave 6, while high trust in the Whitehouse (aOR = 0.42, 95 %CI = 0.24–0.74) and belief that China purposely spread the virus (aOR = 0.66, 95 %CI = 0.46–0.96) at baseline reduced the odds of vaccination. In the adjusted model of vaccination uptake at wave 7, increased age was associated with positive vaccination status, and Black race (compared to white) was associated with negative vaccination status. High trust in the CDC and mainstream news outlets at baseline were both associated with being vaccinated at wave 7, while high trust in the Whitehouse (aOR = 0.24, 95 %CI = 0.11–0.51) and belief that the virus was spread purposefully by China (aOR = 0.60, 95 %CI = 0.39–0.93) were negatively associated with vaccination.ConclusionsThese findings indicated that vaccine uptake could be predicted over a year earlier. Trust in specific sources of COVID-19 information were strong predictors, suggesting that future pandemic preparedness plans should include forums for news media, public health officials, and diverse political leaders to meet and develop coherent plans to communicate to the public early in a pandemic so that antivaccine attitudes do not flourish and become reinforced.     

COVID-19 outbreak in an elderly care home: Very low vaccine effectiveness and late impact of booster vaccination campaign

BackgroundElderly people in long-term care facilities (LTCF) are at higher risk for (severe) COVID-19, yet evidence of vaccine effectiveness (VE) in this population is scarce. In November 2021 (Delta period), a COVID-19 outbreak occurred at a LTCF in the Netherlands, continuing despite measures and booster vaccination campaign. We investigated the outbreak to assess VE of primary COVID-19 vaccination against SARS-CoV-2 infection and mortality, and to describe the impact of the booster vaccination.MethodsWe calculated attack rate (AR) and case fatality (CF) per vaccination status (unvaccinated, primarily vaccinated and boostered). We calculated VE – at on average 6 months after vaccination – as 1- risk ratio (RR) using the crude risk ratio (RR) with 95% confidence intervals (CI) for the association between vaccination status (primary vaccination versus unvaccinated) and outcomes (SARS-CoV-2 infection and mortality < 30 days after testing positive for SARS-CoV-2).ResultsThe overall AR was 67% (70/105). CF was 33% (2/6) among unvaccinated cases, 12% among primarily vaccinated (7/58) and 0% (0/5) among boostered. The VE of primary vaccination was 17% (95% CI ?28%; 46%) against SARS-CoV-2 infection and 70% (95% CI ?44%; 96%) against mortality. Among boostered residents (N = 55), there were 25 cases in the first week after receiving the booster dose, declining to 5 in the second and none in the third week.ConclusionVE of primary vaccination in residents of LTCF was very low against SARS-CoV-2 infection and moderate against mortality. There were few cases at 2 weeks after the booster dose and no deaths, despite the presence of susceptible residents. These data are consistent with the positive impact of the booster vaccination in curbing transmission. Timely booster vaccination in residents of LTCF is therefore important.     

Make it or break it: On-time vaccination intent at the time of Covid-19

On-time effective vaccination is critical to curbing a pandemic, but this is often hampered by citizens' hesitancy to get quickly vaccinated. This research concentrates on the hypothesis that, besides traditional factors in the literature, vaccination success would hinge on two dimensions: a) addressing a broader set of risk perception factors than health-related issues only, and b) securing sufficient social and institutional trust at the time of vaccination campaign launch. We test this hypothesis regarding Covid-19 vaccination preferences in six European countries and at the early stage of the pandemic by April 2020. We find that addressing the two roadblock dimensions could further boost Covid-19 vaccination coverage by 22%. The study also offers three extra innovations. The first is that the traditional segmentation logic between vaccine “acceptors”, “hesitants” and “refusers” is further justified by the fact that segments have different attitudes: refusers care less about health issues than they are worried about family tensions and finance (dimension 1 of our hypothesis). In contrast, hesitants are the battlefield for more transparency by media and government actions (dimension 2 of our hypothesis). The second added value is that we extend our hypothesis testing with a supervised non-parametric machine learning technique (Random Forests). Again, consistent with our hypothesis, this method picks up higher-order interaction between risk and trust variables that strongly predict on-time vaccination intent. We finally explicitly adjust survey responses to account for possible reporting bias. Among others, vaccine-reluctant citizens may under-report their limited will to get vaccinated.     

Effectiveness of the Comirnaty and the Vaxzevria vaccines in preventing SARS-CoV-2 infection among residents in Lazio region (Italy)

We estimated the effectiveness of Comirnaty and Vaxzevria vaccines among 371,423 residents in Lazio Region (Italy) vaccinated since 27/12/2020, and followed until diagnosis of SARS-CoV-2 infection or 25/4/2021, whichever came first. By the end of follow-up most of the Comirnaty-cohort (60%) had received the second dose at recommended time of 21 days (98%), while the Vaxzevria-cohort had received only one dose. Adjusted hazard ratios of SARS-CoV-2 infection at weekly intervals since the first dose were estimated through a Cox regression model using 0–13 days as reference time-interval. An increase in effectiveness with increasing time since administration was observed for Comirnaty (five-weeks = 81%, 95 %CI 71–88%; three-months = 94%, 95 %CI 84–98%). One dose of Vaxzevria showed an effectiveness of 63% (95 %CI 25–82%) after 7 weeks, although further analyses are needed after complete vaccination with two doses. These results could support the ongoing vaccination campaign by reinforcing evidence-based communication aimed at reducing vaccine hesitancy.     

Vaccine effectiveness and duration of protection of COVID-19 mRNA vaccines against Delta and Omicron BA.1 symptomatic and severe COVID-19 outcomes in adults aged 50 years and over in France

The emergence of SARS-CoV-2 variants calls for continuous monitoring of vaccine effectiveness (VE). We estimated the absolute effectiveness of complete 2-dose primary vaccination and booster vaccination with COVID-19 mRNA vaccines, and the duration of protection against Delta and Omicron BA.1 symptomatic infection and severe outcomes. French residents aged ≥50 years, who presented with SARS-CoV-2-like symptoms and tested for SARS-CoV-2 between June 6, 2021 and February 10, 2022 were included. A test-negative study was conducted to estimate VE against symptomatic infection, using conditional logistic regression models. Cox proportional hazard regressions were performed to assess additional protection against severe COVID-19 outcomes (any hospitalization, and intensive care units [ICU] admission or in-hospital death). In total, 273 732 cases and 735 919 controls were included. VE against symptomatic infection after 2-doses vaccination was 86% (95% CI: 75–92%) for Delta and 70% (58–79%) for Omicron, 7–30 days post vaccination. Protection waned over time, reaching 60% (57–63%) against Delta and 20% (16.–24%) for Omicron BA.1 > 120 days after vaccination. The booster dose fully restored protection against symtpomatic Delta infection (95% [81–99%]) but only partially against symptomatic Omicron BA.1 infection (63% [59–67%]). VE against Delta-related severe outcomes was above 95% with 2 doses, and persisted for at least four months. Protection against any Omicron BA.1-hospitalization was 92% (65%-99%) at 8–30 days, and 82% (67%-91%) > 120 days from the second dose. Against BA.1 ICU admission or in-patient death, VE stood at 98% (0–100%) at 8–30 days, and was 90% (40–99%) > 120 days from the second dose. Protection confered by mRNA vaccines against severe disease caused by either Delta or Omicron BA.1 appeared high and sustained over time. Protection against symptomatic diseases after 2 doses decreased rapidly, especially against Omicron BA.1. A booster dose restored high protection against Delta but only a partial one against Omicron BA.1.     

From COVID-19 vaccine candidates to compulsory vaccination: The attitudes of Italian citizens in the key 7-month of vaccination campaign

IntroductionThe aim of the study is to understand the evolution of COVID-19 vaccine acceptance over the key 7-month vaccine campaign in Italy, a period in which the country moved from candidate vaccines to products administered to the public. The research focus points to evaluate COVID-19 vaccine attitudes in adults and their children, propension towards compulsory vaccination, past and present adherence to anti-flu and anti-pneumococcal vaccines, and the reasons for trust/mistrust of vaccines.MethodsItalian residents aged 16->65 years were invited to complete an online survey from September 2020 to April 2021. The survey contained 13 questions: 3 on demographic data; 8 on vaccine attitudes; and 2 open-ended questions about the reasons of vaccine confidence/refusal. A preliminary word frequency analysis has been conducted, as well as a statistical bivariate analysis.ResultsOf 21.537 participants, the confidence of those in favor of the COVID-19 vaccine increases of 50 % and the number of people who wanted more information decreases by two-third. Willingness to vaccinate their children against COVID-19 also increased from 51 % to 66.5 %. Only one-third of the strong vaccine-hesitant participants, i.e. 10 %, remained hostile. Compulsory vaccination showed a large and increasing favor by participants up to 78 %, in a way similar to their propensity for children’s mandatory vaccination (70.6 %). Respondents’ past and present adherence to anti-flu and anti-pneumococcal vaccines does not predict their intentions to vaccinate against COVID-19. Finally, a semantic analysis of the reasons of acceptance/refusal of COVID-19 vaccination suggests a complex decision-making process revealed by the participants’ use of common words in pro-and-cons arguments.ConclusionThe heterogeneity in the COVID-19 vaccine hesitancy, determinants and opinions detected at different ages, genders and pandemic phases suggests that health authorities should avoid one-size-fits-all vaccination campaigns. The results emphasize the long-term importance of reinforcing vaccine information, communication and education needs.     

Relationship between double COVID-19 vaccine uptake and trust in effectiveness and safety of vaccination in general in 23 Member states of the European Union: an ecological study

IntroductionThe aim of this study was to assess the relationship between double COVID-19 vaccine uptake and trust in effectiveness and safety of vaccination in general in 23 European Union (EU) countries.MethodsEcological study. Data was retrieved from the Flash Eurobarometer 494 and Our World in Data. We estimated Pearson’s correlation coefficients and fitted multiple linear regression models.ResultsThere is a negative linear correlation between the percentage of people doubly vaccinated and the percentage of low trust in vaccine effectiveness (r = -0.48, p-value = 0.021), and the percentage of low trust in vaccine safety (r = -0.43, p-value = 0.041). There is a negative adjusted relation between the percentage of low trust in vaccine safety and the percentage of people doubly vaccinated (aβ_{% low trust in vaccine safety}:-0.25; 95% CI: ?0.49,-0.01, p-value = 0.045).ConclusionAn increase in health literacy of people living in certain countries in the EU may be needed to boost COVID-19 vaccine uptake.     

Assessing COVID-19 vaccine effectiveness against Omicron subvariants: Report from a meeting of the World Health Organization

Emerging in November 2021, the SARS-CoV-2 Omicron variant of concern exhibited marked immune evasion resulting in reduced vaccine effectiveness against SARS-CoV-2 infection and symptomatic disease. Most vaccine effectiveness data on Omicron are derived from the first Omicron subvariant, BA.1, which caused large waves of infection in many parts of the world within a short period of time. BA.1, however, was replaced by BA.2 within months, and later by BA.4 and BA.5 (BA.4/5). These later Omicron subvariants exhibited additional mutations in the spike protein of the virus, leading to speculation that they might result in even lower vaccine effectiveness. To address this question, the World Health Organization hosted a virtual meeting on December 6, 2022, to review available evidence for vaccine effectiveness against the major Omicron subvariants up to that date. Data were presented from South Africa, the United Kingdom, the United States, and Canada, as well as the results of a review and meta-regression of studies that evaluated the duration of the vaccine effectiveness for multiple Omicron subvariants. Despite heterogeneity of results and wide confidence intervals in some studies, the majority of studies showed vaccine effectiveness tended to be lower against BA.2 and especially against BA.4/5, compared to BA.1, with perhaps faster waning against severe disease caused by BA.4/5 after a booster dose. The interpretation of these results was discussed and both immunological factors (i.e., more immune escape with BA.4/5) and methodological issues (e.g., biases related to differences in the timing of subvariant circulation) were possible explanations for the findings. COVID-19 vaccines still provide some protection against infection and symptomatic disease from all Omicron subvariants for at least several months, with greater and more durable protection against severe disease.     

Immunological responses and adverse reactions of the heterologous second booster dose of BNT162b2 after two-dose CoronaVac for COVID-19 vaccination in healthcare workers of Faculty of Medicine,Naresuan University

BackgroundThe first COVID-19 vaccination campaign in Thailand began in April 2020, with healthcare workers receiving two doses of inactivated COVID-19 vaccine (CoronaVac). However, the emergence of the delta and omicron variants raised concerns about vaccine effectiveness. The Thai Ministry of Public Health provided the first booster dose (third dose) and second booster dose (fourth dose) of the mRNA vaccine (BNT162b2) for healthcare workers. This study investigated the immunity and adverse reactions elicited by a heterologous second booster dose of BNT162b2 after a two-dose CoronaVac vaccination for COVID-19 in healthcare workers of the Faculty of Medicine, Naresuan University.MethodsIgG titres against the SARS-CoV-2-spike protein were measured four and 24 weeks after the second booster dose of BNT162b2 in the study participants. Adverse reactions were recorded during the first three days, four weeks and 24 weeks after the second booster dose of BNT162b2.ResultsIgG against the SARS-CoV-2-spike protein was positive (>10 U/ml) in 246 of 247 participants (99.6 %) at both four and 24 weeks after the second booster dose of BNT162b2. The median specific IgG titres at four and 24 weeks after the second booster dose of BNT162b2 were 299 U/ml (min: 2, max: 29,161) and 104 U/ml (min: 1, max: 17,920), respectively. The median IgG level declined significantly 24 weeks after the second booster dose of the BNT162b2 vaccine. Of the 247 participants, 179 (72.5 %) experienced adverse reactions in the first three days after the second booster dose of BNT162b2. Myalgia, fever, headache, injection site pain and fatigue were the most common adverse reactions.ConclusionThis study demonstrated that a heterologous second booster dose of BNT162b2 after two doses of CoronaVac induced elevated IgG against the SARS-CoV-2-spike protein and caused minor adverse reactions in healthcare workers of the Faculty of Medicine, Naresuan University.This study was registered as Thailand Clinical Trials No. TCTR20221112001.     

SARS-CoV-2 outbreak in a nursing home after vaccination with BNT162b2: A role for the quantification of circulating antibodies

We describe an outbreak of SARS-CoV-2 (B.1.351) in a nursing home. At the outbreak onset 96% of residents and 76% of HCW had received two doses of BNT162b2. Twenty-eight residents (28/53) and six HCW (6/33) were infected. Infected residents had lower levels of anti-S antibodies compared to those who were not infected (157 vs 552 U/mL). Among 50 residents with available serological status, nineteen (19/25) with serum concentration < 300 U/mL and seven (7/25) with concentration > 300 U/mL acquired SARS-CoV-2 (RR 2.7 [95 %CI 1.4–5.3]). The quantification of circulating antibodies could be useful in detecting people with an impaired immune response who are at high risk of acquiring and spreading SARS-CoV-2.     

The potential public health and economic value of a hypothetical COVID-19 vaccine in the United States: Use of cost-effectiveness modeling to inform vaccination prioritization

BackgroundResearchers are working at unprecedented speed to develop a SARS-CoV-2 vaccine. We aimed to assess the value of a hypothetical vaccine and its potential public health impact when prioritization is required due to supply constraints.MethodsA Markov cohort model was used to estimate COVID-19 related direct medical costs and deaths in the United States (US), with and without implementation of a 60% efficacious vaccine. To prioritize the vaccine under constrained supply, the population was divided into tiers based on age; risk and age; and occupation and age; and outcomes were compared across one year under various supply assumptions. The incremental cost per quality-adjusted life-year (QALY) gained versus no vaccine was calculated for the entire adult population and for each tier in the three prioritization schemes.ResultsThe incremental cost per QALY gained for the US adult population was $8,200 versus no vaccination. For the tiers at highest risk of complications from COVID-19, such as those ages 65 years and older, vaccination was cost-saving compared to no vaccination. The cost per QALY gained increased to over $94,000 for those with a low risk of hospitalization and death following infection. Results were most sensitive to infection incidence, vaccine price, the cost of treating COVID-19, and vaccine efficacy. Under the most optimistic supply scenario, the hypothetical vaccine may prevent 31% of expected deaths. As supply becomes more constrained, only 23% of deaths may be prevented. In lower supply scenarios, prioritization becomes more important to maximize the number of deaths prevented.ConclusionsA COVID-19 vaccine is predicted to be good value for money (cost per QALY gained <$50,000). The speed at which an effective vaccine can be made available will determine how much morbidity and mortality may be prevented in the US.     

Influenza vaccination in the time of COVID-19: A national U.S. survey of adults

IntroductionDecisions about influenza vaccination for fall-winter 2020 were made against the backdrop of the COVID-19 pandemic. During May 2020, the authors examined intended vaccination in the next 12 months in relationship to demographic variables, healthcare attitudes, and personal COVID-19 experiences for two samples of adults--those who did not receive influenza vaccine during the prior 12 months, and those who did.MethodsIn May 2020, a cross-sectional online survey was conducted with a national US sample. Participants reported prior influenza vaccination (yes/no during prior 12 months) and anticipated vaccination (yes/no during next 12 months). Covariates included demographic characteristics (e.g., gender, race-ethnicity, political ideology), general beliefs (e.g., benefits of vaccines, altruistic attitudes), and COVID-19 health beliefs and experiences (COVID-19 worry and severity, perception of COVID-19 as a community threat, knowing someone with COVID-19). For each group, hierarchical multivariable logistic regression was conducted with intent to vaccinate as the outcome.ResultsAmong participants (n = 3502), 47% did not receive influenza vaccine in the prior 12 months and 53% had; 25.5% of non-vaccinators and 91.9% of vaccinators intended future vaccination. For non-vaccinators, odds of intending vaccination was associated with race/ethnicity (Hispanics were more likely to intend than white-NH; AOR = 1.74; 95% CI = 1.23–2.4), greater perceived benefits of vaccination (AOR = 2.19; 95% CI = 1.88–2.54), and perception of COVID-19 as a community threat (AOR = 1.91; 95% CI = 1.49–2.45). For vaccinators, odds of intending vaccination was associated with age (AOR = 1.04; 95% CI = 1.03–1.05), race/ethnicity (Black-NH and Other-NH were less likely to intend than white-NH, AOR = 0.60; 95% CI = 0.36–0.999; and AOR = 0.45; 95% CI = 0.24–0.84, respectively), greater perceived benefits of vaccination (AOR = 1.88; 95% CI = 1.45–2.45) and greater perception of collective benefits of vaccines (AOR = 1.48; 95% CI = 1.15–1.90).ConclusionsThe COVID-19 pandemic may have served as a cue to action for influenza vaccination intention among some prior non-vaccinators whereas intention among prior vaccinators is more related to positive attitudes toward vaccination.     

A phase 1/2 randomised placebo-controlled study of the COVID-19 vaccine mRNA-1273 in healthy Japanese adults: An interim report

IntroductionThe mRNA vaccine, mRNA-1273/TAK-919, encodes the prefusion-stabilised spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report interim results of the first study evaluating safety and immunogenicity of mRNA-1273 in healthy Japanese participants.MethodsThis phase 1/2, randomised, observer-blind, placebo-controlled trial, conducted in Japan (two sites), enrolled healthy adults aged ≥ 20 years with no prior exposure to investigational coronavirus vaccines/treatments, and no known history/risk of SARS-CoV-2 infection. Participants were stratified by age (< 65/≥ 65 years) and randomised to receive two doses of 100 μg mRNA-1273 or placebo administered as intramuscular injections 28 days apart. Primary outcomes were safety and immunogenicity assessed by anti-SARS-CoV-2-spike protein-binding antibody level (bAb). A secondary outcome was SARS-CoV-2 neutralising antibody (nAb) response.ResultsParticipants were enrolled between 21 January and 3 February 2021, and 200 were randomised: mRNA-1273, n = 150 (< 65 years, n = 100; ≥ 65 years, n = 50); placebo, n = 50 (< 65 years, n = 40; ≥ 65 years, n = 10). Solicited adverse events (AEs) through 7 days after each vaccination occurred in 144/150 (96%) and 19/50 (38%) participants in the mRNA-1273 and placebo arms, respectively. In the mRNA-1273 arm, injection-site pain, myalgia and fatigue were the most frequently reported solicited AEs after each vaccination, irrespective of age. Robust immune responses occurred with mRNA-1273 (n = 147) with a bAb geometric mean fold rise (95% confidence interval [CI]) from baseline of 1009 (865, 1177) and a nAb of 21.7 (19.8, 23.8) at day 57. Seroconversion rates (95% CI) for bAb and nAb were both 100% (97.5, 100) at day 57. No such response occurred with placebo (n = 49).ConclusionTwo doses of 100 μg mRNA-1273 given 28 days apart demonstrated an acceptable safety profile and induced significant anti-SARS-CoV-2 immune responses in a Japanese population aged ≥ 20 years. Funding: Takeda Pharmaceutical Company Limited and Japan Agency for Medical Research and Development (AMED). ClinicalTrials.gov: NCT04677660.     

Role of anti-polyethylene glycol (PEG) antibodies in the allergic reactions to PEG-containing Covid-19 vaccines: Evidence for immunogenicity of PEG

A small fraction of recipients who receive polyethylene-glycol (PEG)-containing COVID-19 mRNA-LNP vaccines (Comirnaty and Spikevax) develop hypersensitivity reactions (HSRs) or anaphylaxis. A causal role of anti-PEG antibodies (Abs) has been proposed, but not yet been proven in humans. We used ELISA for serial measurements of SARS-CoV-2 neutralizing Ab (anti-S) and anti-PEG IgG/IgM Ab levels before and after the first and subsequent booster vaccinations with mRNA-LNP vaccines in a total of 291 blood donors. The HSRs in 15 subjects were graded and correlated with anti-PEG IgG/IgM, just as the anti-S and anti-PEG Ab levels with each other. The impacts of gender, allergy, mastocytosis and use of cosmetics were also analyzed. Serial testing of two or more plasma samples showed substantial individual variation of anti-S Ab levels after repeated vaccinations, just as the levels of anti-PEG IgG and IgM, which were over baseline in 98–99 % of unvaccinated individuals. About 3-4 % of subjects in the strongly left-skewed distribution had 15–45-fold higher values than the median, referred to as anti-PEG Ab supercarriers. Both vaccines caused significant rises of anti-PEG IgG/IgM with >10-fold rises in about ∼10 % of Comirnaty, and all Spikevax recipients. The anti-PEG IgG and/or IgM levels in the 15 vaccine reactors (3 anaphylaxis) were significantly higher compared to nonreactors. Serial testing of plasma showed significant correlation between the booster injection-induced rises of anti-S and anti-PEG IgGs, suggesting coupled anti-S and anti-PEG immunogenicity. Conclusions: The small percentage of people who have extreme levels of anti-PEG Ab in their blood may be at increased risk for HSRs/anaphylaxis to PEGylated vaccines and other PEGylated injectables. This risk might be further increased by the anti-PEG immunogenicity of these vaccines. Screening for anti-PEG Ab “supercarriers” may help predicting reactors and thus preventing these adverse phenomena.     

Relative effectiveness of a 2nd booster dose of COVID-19 mRNA vaccine up to four months post administration in individuals aged 80 years or more in Italy: A retrospective matched cohort study

Several countries started a 2nd booster COVID-19 vaccination campaign targeting the elderly population, but evidence around its effectiveness is still scarce. This study aims to estimate the relative effectiveness of a 2nd booster dose of COVID-19 mRNA vaccine in the population aged ≥ 80 years in Italy, during predominant circulation of the Omicron BA.2 and BA.5 subvariants.We linked routine data from the national vaccination registry and the COVID-19 surveillance system. On each day between 11 April and 6 August 2022, we matched 1:1, according to several demographic and clinical characteristics, individuals who received the 2nd booster vaccine dose with individuals who received the 1st booster vaccine dose at least 120 days earlier. We used the Kaplan-Meier method to compare the risks of SARS-CoV-2 infection and severe COVID-19 (hospitalisation or death) between the two groups, calculating the relative vaccine effectiveness (RVE) as (1 – risk ratio)X100.Based on the analysis of 831,555 matched pairs, we found that a 2nd booster dose of mRNA vaccine, 14–118 days post administration, was moderately effective in preventing SARS-CoV-2 infection compared to a 1st booster dose administered at least 120 days earlier [14.3 %, 95 % confidence interval (CI): 2.2–20.2]. RVE decreased from 28.5 % (95 % CI: 24.7–32.1) in the time-interval 14–28 days to 7.6 % (95 % CI: ?14.1 to 18.3) in the time-interval 56–118 days. However, RVE against severe COVID-19 was higher (34.0 %, 95 % CI: 23.4–42.7), decreasing from 43.2 % (95 % CI: 30.6–54.9) to 27.2 % (95 % CI: 8.3–42.9) over the same time span.Although RVE against SARS-CoV-2 infection was much reduced 2–4 months after a 2nd booster dose, RVE against severe COVID-19 was about 30 %, even during prevalent circulation of the Omicron BA.5 subvariant. The cost-benefit of a 3rd booster dose for the elderly people who received the 2nd booster dose at least four months earlier should be carefully evaluated.     

Evaluation of potential adverse events following COVID-19 mRNA vaccination among adults aged 65 years and older: Two self-controlled studies in the U.S.

BackgroundOur near-real-time safety monitoring of 16 adverse events (AEs) following COVID-19 mRNA vaccination identified potential elevation in risk for six AEs following primary series and monovalent booster dose administration. The crude association with AEs does not imply causality. Accordingly, we conducted robust evaluation of potential associations.MethodsWe conducted two self-controlled case series studies of COVID-19 mRNA vaccines (BNT162b2 and mRNA-1273) in U.S. Medicare beneficiaries aged ≥ 65 years. Adjusted incidence rate ratio (IRRs) and 95 % confidence intervals (CIs) were estimated following primary series doses for acute myocardial infarction (AMI), pulmonary embolism (PE), immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC); and following monovalent booster doses for AMI, PE, ITP, Bell’s Palsy (BP) and Myocarditis/Pericarditis (Myo/Peri).ResultsThe primary series study included 3,360,981 individuals who received 6,388,542 primary series doses; the booster study included 6,156,100 individuals with one monovalent booster dose. The AMI IRR following BNT162b2 primary series and booster was 1.04 (95 % CI: 0.91 to 1.18) and 1.06 (95 % CI: 1.003 to 1.12), respectively; for mRNA-1273 primary series and booster, 1.01 (95 % CI: 0.82 to 1.26) and 1.05 (95 % CI: 0.998 to 1.11), respectively. The hospital inpatient PE IRR following BNT162b2 primary series and booster was 1.19 (95 % CI: 1.03 to 1.38) and 0.86 (95 % CI: 0.78 to 0.95), respectively; for mRNA-1273 primary series and booster, 1.15 (95 % CI: 0.94 to 1.41) and 0.87 (95 % CI: 0.79 to 0.96), respectively. The studies’ results do not support that exposure to COVID-19 mRNA vaccines elevate the risk of ITP, DIC, Myo/Peri, and BP.ConclusionWe did not find an increased risk for AMI, ITP, DIC, BP, and Myo/Peri and there was not consistent evidence for PE after exposure to COVID-19 mRNA primary series or monovalent booster vaccines. These results support the favorable safety profile of COVID-19 mRNA vaccines administered in the U.S. elderly population.